Baszler T V, Long M T, McElwain T F, Mathison B A
Department of Veterinary Microbiology and Pathology, Washington State University, Pullman 99164-7040, USA.
Int J Parasitol. 1999 Oct;29(10):1635-46. doi: 10.1016/s0020-7519(99)00141-1.
The type of immune response required to protect mice against clinical disease during acute Neospora caninum challenge was investigated in BALB/c mice. Groups of female BALB/c mice were infected i.p. with N. caninum tachyzoites concomitant with either: (1) antibody to interferon-gamma; (2) recombinant murine interleukin-12; or (3) recombinant murine interleukin-12 plus antibody to interferon-gamma. Mice treated with anti-interferon-gamma alone had increased morbidity/mortality, decreased body weight, increased foci of liver necrosis and increased numbers of N. caninum tachyzoites in the lung by 7 days p.i. compared with controls. Increased disease and parasite load in the anti-interferon-gamma-treated mice was associated with antigen-specific antibody IgG1 > IgG2a and a three-fold decreased ratio of antigen-specific interferon-gamma:interleukin-4. Mice treated with recombinant murine interleukin-12 had decreased encephalitis and brain parasite load at 3 weeks p.i. compared with control mice treated with PBS. In recombinant murine interleukin-12-treated mice, decreased brain lesions and parasite load were associated with antigen-specific antibody IgG2a > IgG1 and a three-fold increased ratio of antigen-specific interferon-gamma:interleukin-4 from splenocytes; the interleukin-12 effect was dependent upon interferon-gamma, as indicated by concomitant in vivo interferon-gamma neutralisation. By 6 weeks p.i. with N. caninum, there were no differences in brain lesions and parasite load between interleukin-12- and PBS-treated groups, indicating that the effects of interleukin-12 on driving a protective type 1 response were transient. These data indicate a role for interferon-gamma, interleukin-12 and type 1 immune responses in control of acute neosporosis in mice.
在BALB/c小鼠中研究了在急性犬新孢子虫攻击期间保护小鼠免受临床疾病所需的免疫反应类型。将雌性BALB/c小鼠分组，腹腔注射犬新孢子虫速殖子，同时给予以下物质：(1)抗干扰素-γ抗体；(2)重组鼠白细胞介素-12；或(3)重组鼠白细胞介素-12加抗干扰素-γ抗体。与对照组相比，单独用抗干扰素-γ治疗的小鼠在感染后7天时发病率/死亡率增加、体重减轻、肝坏死灶增多且肺中犬新孢子虫速殖子数量增加。抗干扰素-γ治疗的小鼠疾病和寄生虫负荷增加与抗原特异性抗体IgG1 > IgG2a以及抗原特异性干扰素-γ:白细胞介素-4的比例降低三倍有关。与用PBS治疗的对照小鼠相比，用重组鼠白细胞介素-12治疗的小鼠在感染后3周时脑炎和脑寄生虫负荷降低。在重组鼠白细胞介素-12治疗的小鼠中，脑损伤和寄生虫负荷降低与抗原特异性抗体IgG2a > IgG1以及脾细胞中抗原特异性干扰素-γ:白细胞介素-4的比例增加三倍有关；白细胞介素-12的作用依赖于干扰素-γ，体内干扰素-γ中和实验表明了这一点。到犬新孢子虫感染后6周时，白细胞介素-12治疗组和PBS治疗组之间的脑损伤和寄生虫负荷没有差异，这表明白细胞介素-12驱动保护性1型反应的作用是短暂的。这些数据表明干扰素-γ、白细胞介素-12和1型免疫反应在控制小鼠急性新孢子虫病中起作用。
